Cd1d-dependent regulation of bacterial colonization in the intestine of mice

Nieuwenhuis, Edward E. S.; Matsumoto, Tetsuya; Lindenbergh, Dicky; Willemsen, Rob; Kaser, Arthur; Simons-Oosterhuis, Ytje; Brugman, Sylvia; Yamaguchi, Keizo; Ishikawa, Hajime; Aiba, Yuji; Koga, Yuichi; Samsom, Janneke N.; Oshima, Koichiro; Kikuchi, Mami; Escher, Johanna C.; Hattori, Masahira; Onderdonk, Andrew B.; Blumberg, Richard S.

doi:10.1172/jci36509

Cited by 146 publications

(143 citation statements)

References 59 publications

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“…4 These findings are in agreement with those of a previous study on Paneth cell function in vivo, in which Vaishnava et al 3 elegantly showed the crucial role of Paneth cells in limiting translocation of commensal and pathogenic bacteria across the intestinal barrier in a Paneth cell ablation model. In addition, Nieuwenhuis et al 33 associated Paneth cell granule abnormalities with alterations in the composition of the intestinal microbiota and bacteria that moved into close proximity with epithelial cells.…”

Section: Starvation Compromises Paneth Cells 2889mentioning

confidence: 99%

Starvation Compromises Paneth Cells

Hodin

Lenaerts

Grootjans

et al. 2011

The American Journal of Pathology

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The intestine is challenged with the task of protecting the body's internal milieu against bacterial invasion. To this end, the gut is equipped with an epithelial lining connected by tight junctions, a mucus layer, gut-associated lymphoid tissue, and Paneth cells. Paneth cells are highly specialized epithelial cells located in the crypts of the small intestine, and play an important role in gut innate immunity. 1 These cells sense bacterial presence and secrete granules containing antimicrobial peptides, including lysozyme, RegIII␥, and cryptdins (the murine counterparts of human ␣-defensins) both constitutively and in response to activation by bacteria or their products. 2 Using a murine cell ablation model, Paneth cells were shown to be crucial in host protection against invasion of both commensal and pathogenic microbiota. 3 In addition, our group has recently shown the additive importance of Paneth cells in preventing bacterial translocation in situations of physical intestinal barrier loss. 4 Enteral starvation and total parenteral nutrition, as applied to critically ill patients, are reported to result in increased gut wall permeability, a compromised immune system, and bacterial translocation. 5-10 Because autophagy, a process induced on starvation, 11-13 influences the generation of Paneth cell granules, 14 we hypothesize that enteral starvation impairs Paneth cell function, contributing to starvation-associated gut compromise.In this study, the effects of food deprivation on Paneth cell function were investigated using a mouse starvation model. We provide evidence that lack of enteral feeding results in Paneth cell autophagy, decreased expression of antimicrobial products (ie, lysozyme, cryptdin, and RegIII␥), and the presence of atypical secretory granules. Our results propose compromised Paneth cells to be involved in the reduced protection against bacterial translocation in enteral starvation.

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Section: Starvation Compromises Paneth Cells 2889mentioning

confidence: 99%

Starvation Compromises Paneth Cells

Hodin

Lenaerts

Grootjans

et al. 2011

The American Journal of Pathology

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“…1C). These findings indicate that CLP-induced sepsis is attenuated in NKT-cell-deficient mice.NKT cells and CD1d were reported to regulate bacterial colonization in the mouse intestine, resulting in prominent differences in the composition of intestinal microbiota in CD1d −/− vs. WT mice in specific pathogen-free conditions [22]. Thus, differences in the cecal bacterial composition of WT and CD1d −/− might affect the development and progression of sepsis in these mice.…”

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confidence: 99%

IFN‐γ‐producing NKT cells exacerbate sepsis by enhancing C5a generation via IL‐10‐mediated inhibition of CD55 expression on neutrophils

Kim

Ahn

et al. 2014

Eur J Immunol

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A role for NKT cells has been implicated in sepsis, but the mechanism by which NKT cells contribute to sepsis remains unclear. Here, we examined WT and NKT-cell-deficient mice of C57BL/6 background during cecal ligation and puncture-induced sepsis. The levels of C5a, IFN-γ, and IL-10 were higher in the serum and peritoneal fluid of WT mice than in those of CD1d −/− mice, while the mortality rate was lower in CD1d −/− mice than in WT mice. C5a blockade decreased mortality of WT mice during sepsis, whereas it did not alter that of CD1d −/− mice. As assessed by intracellular staining, NKT cells expressed IFN-γ, while neutrophils expressed IL-10. Upon coculture, IL-10-deficient NKT cells enhanced IL-10 production by WT, but not IFN-γR-deficient, neutrophils. Meanwhile, CD1d −/− mice exhibited high CD55 expression on neutrophils during sepsis, whereas those cells from WT mice expressed minimal levels of CD55. Recombinant IL-10 administration into CD1d −/− mice reduced CD55 expression on neutrophils. Furthermore, adoptive transfer of sorted WT, but not IFN-γ-deficient, NKT cells into CD1d −/− mice suppressed CD55 expression on neutrophils, but increased IL-10 and C5a levels. Taken together, IFN-γ-producing NKT cells enhance C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils, thereby exacerbating sepsis.Keywords: C5a r IFN-γ r Neutrophils r NKT cell r Sepsis Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNKT cells are a distinct T-cell subset characterized by the expression of natural killer receptors and semi-invariant TCRs. These cells recognize glycolipids presented by CD1d, an MHC class I-like Correspondence: Dr. Doo Hyun Chung e-mail: doohyun@snu.ac.kr protein expressed by APCs [1]. During bacterial infection, TCRs on NKT cells directly recognize glycolipids derived from certain Gramnegative bacterial membranes [2,3] and can be activated by innate cytokines secreted by dendritic cells that have been activated by microorganisms [2,4]. Furthermore, LPS-mediated engagement of TLR4 directly activates NKT cells in terms of differential * These authors contributed equally to this work. Eur. J. Immunol. 2014Immunol. . 44: 2025Immunol. -2035 cytokine production, thereby regulating immune diseases [5]. These findings suggest that NKT cells, activated during immune responses against bacteria, regulate bacteria-mediated pathologic processes such as sepsis. Sepsis is a complex inflammatory dysregulation that causes multiple organ dysfunction and coagulopathy, often resulting in death [6,7]. Several studies have demonstrated that NKT cells promote LPS-or cecal ligation and puncture (CLP)-induced sepsis in mice through the production of . Consistent with these findings, two independent studies have demonstrated that treatment of C57BL/6 mice with anti-CD1d antibody enhances survival rates during CLP-induced sepsis [11,12], suggesting that NKT-cell-mediated promotion of sepsis depends on an interaction between CD1d and TCR...

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“…For example, it was shown that CD1d-deficient mice lacking NKT-cells display differences in intestinal microbial composition resulting from altered Paneth cell function. 23 These data suggest a role for specific subsets of T lymphocytes in the establishment of intestinal microbiota. Furthermore, certain bacteria are able to induce regulatory T lymphocytes 24,25 and large numbers of intra-epithelial lymphocytes reside within the epithelial cell layer that separates the underlying mucosa from the intestinal lumen, suggesting an important role in maintaining intestinal homeostasis with the microbiota.…”

Section: Introductionmentioning

confidence: 89%

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

et al. 2014

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Abbreviations: wpf: weeks post fertilization.Dysbiosis of the intestinal microbial community is considered a risk factor for development of chronic intestinal inflammation as well as other diseases such as diabetes, obesity and even cancer. Study of the innate and adaptive immune pathways controlling bacterial colonization has however proven difficult in rodents, considering the extensive cross-talk between bacteria and innate and adaptive immunity. Here, we used the zebrafish to study innate and adaptive immune processes controlling the microbial community. Zebrafish lack a functional adaptive immune system in the first weeks of life, enabling study of the innate immune system in the absence of adaptive immunity. We show that in wild type zebrafish, the initial lack of adaptive immunity associates with overgrowth of Vibrio species (a group encompassing fish and human pathogens), which is overcome upon adaptive immune development. In Rag1-deficient zebrafish (lacking adaptive immunity) Vibrio abundance remains high, suggesting that adaptive immune processes indeed control Vibrio species. Using cell transfer experiments, we confirm that adoptive transfer of T lymphocytes, but not B lymphocytes into Rag1-deficient recipients suppresses outgrowth of Vibrio. In addition, ex vivo exposure of intestinal T lymphocytes to Rag1-deficient microbiota results in increased interferon-gamma expression by these T lymphocytes, compared to exposure to wild type microbiota. In conclusion, we show that T lymphocytes control microbial composition by effectively suppressing the outgrowth of Vibrio species in the zebrafish intestine.

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Cd1d-dependent regulation of bacterial colonization in the intestine of mice

Cited by 146 publications

References 59 publications

Starvation Compromises Paneth Cells

Starvation Compromises Paneth Cells

IFN‐γ‐producing NKT cells exacerbate sepsis by enhancing C5a generation via IL‐10‐mediated inhibition of CD55 expression on neutrophils

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

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